The Integrative Physiology Core is designed to conduct in vivo and in vitro experiments to characterize metabolic phenotypes of transgenic/knockout mouse models potentially useful for understanding diabetes, its complications, obesity and related metabolic conditions. The primary purpose of the core is to provide comprehensive standardized procedures, accurate analysis, and assistance in the design of experiments and interpretation of results to better understand the mechanisms of diabetes, its complications, obesity and related metabolic diseases or conditions for NIH grantees and others, both inside and outside Yale, who wish to characterize metabolic and physiologic alterations that may occur in mice. The Integrative Physiology Core provides highly skilled staff and state-of- the-art instrumentation to provide the most accurate, precise and reproducible in vivo glucose-insulin clamp results with the highest success rate. The principal functions of the Integrative Physiology Core are to provide investigators a centralized facility for assessment of: 1) Insulin action and ?-cell function in vivo in awake, unrestrained mice using hyperinsulinemic-euglycemic clamp and hyperglycemic clamps, respectively, 2) Glucose tolerance, 3) Counter-regulatory responses to hypoglycemia, 4) In vivo lipolysis under basal or hyperinsulinemic conditions, 5) Muscle mitochondrial function by 31P and 13C NMR spectroscopy, 6) Effects of exercise/training on glucose metabolism, 7) State-of-the-art metabolic mouse imaging by PET and MRI, 8) Transgenic/knockout mouse activity, food and water consumption, and energy expenditure using comprehensive mouse metabolic cages, 9) Body composition in vivo in mice using 1H NMR spectroscopy, 10) Glucose uptake in muscle and fat, 11) Rates of glucose-stimulated insulin secretion from isolated pancreatic islets, 12) Substrate oxidative and non- oxidative metabolism in mouse mitochondria and isolated cell suspensions, 13) Preparation of mouse tissue extracts and plasma samples for biochemical (GC-MS, LC-MS/MS, NMR) and molecular analysis in collaboration with the Yale MMPC Metabolomics Core, and 14) Assistance in the design of in vivo and in vitro experiments and interpretation of results.